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Monday, March 24, 2014

Gay genes? Yeah, but no, well kind of… but, so what?

Sexual preference is one of the most
strongly genetically determined behavioural traits we know of. A single genetic
element is responsible for most of the variation in this trait across the
population. Nearly all (>95%) of the people who inherit this element are
sexually attracted to females, while about the same proportion of people who do
not inherit it are attracted to males. This attraction is innate, refractory to
change and affects behaviour in stereotyped ways, shaped and constrained by
cultural context. It is the commonest and strongest genetic effect on behaviour
that we know of in humans (in all mammals, actually). The genetic element is of
course the Y chromosome.

The idea that sexual behaviour can be
affected by – even largely determined by – our genes is therefore not only not
outlandish, it is trivially obvious. Yet claims that differences in sexual orientation may have at least a partly
genetic basis seem to provoke howls of scepticism and outrage from many, mostly
based not on scientific arguments but political ones.

The term sexual orientation refers to
whether your sexual preference matches the typical preference based on whether
or not you have a Y chromosome. It is important to realise that it therefore
refers to four different states, not two: (i) has Y chromosome, is attracted to
females; (ii) has Y chromosome, is attracted to males; (iii) does not have Y
chromosome, is attracted to males; (iv) does not have Y chromosome, is attracted
to females. We call two of these states heterosexual and two of them
homosexual. (This ignores the many individuals whose sexual
preferences are not so exclusive or rigid).

A recent twin study confirms that sexual
orientation is moderately heritable – that is, that variation in genes
contributes to variation in this trait. These effects are detected by looking
at pairs of twins and determining how often, when one of them is homosexual,
the other one is too. This rate is much higher (30-50%) in monozygotic, or
identical, twins (who share all of their DNA sequence), than in dizygotic, or
fraternal, twins (who share only half of their DNA), where the rate is 10-20%.
If we assume that the environments of pairs of mono- or dizygotic twins are
equally similar, then we can infer that the increased similarity in sexual
orientation in pairs of monozygotic twins is due to their increased genetic
similarity.

These data are not yet published (or peer
reviewed) but were presented by Dr. Michael Bailey at the recent American
Association for the Advancement of Science meeting (Feb 12th 2014) and widely reported on.
They confirm and extend findings from multiple previous twin studies across
several different countries, which have all found fairly similar results (see here for more details). Overall, the conclusion that sexual orientation is
partly heritable was already firmly made.

The reaction to news of this recent study reveals
a deep disquiet with the idea that homosexuality may arise due to genetic
differences. First, there are those who scoff at the idea that such a complex
behaviour could be determined by what may be only a small number of genetic
differences – perhaps only one. As I recently discussed, this view is based on
a fundamental misunderstanding of what genetic findings really mean. Finding
that a trait (a difference in some
system) can be affected by a single genetic difference does not mean a single
gene is responsible for crafting the entire system – it simply means that the
system does not work normally in the absence of that gene. (Just as a car does
not work well without its steering wheel).

Others have expressed a variety of personal
and political reactions to these findings, ranging from welcoming further
evidence of a biological basis for sexual orientation to worry that it will be
used to label homosexuality a genetic disorder and even to enable selective
abortion based on genetic prediction. The latter possibility may be made more
technically feasible by the other aspect of the recently reported study, which
was the claim that they have mapped genetic variants affecting sexual
orientation to two specific regions of the genome. (This doesn’t mean they have
identified specific genetic variants but may be a step towards doing so).

Let’s explore what the data in this case
really show and really mean. A variety of conclusions can be drawn from this
and previous studies:

1.Differences in sexual
orientation are partly attributable to genetic differences.

2.Sexual orientation in males and
females is controlled by distinct sets of genes. (Dizygotic twins of opposite
sex show no increased similarity in sexual orientation compared to unrelated
people – if a female twin is gay, there is no increased likelihood that her
twin brother will be too, and vice versa).

3.Male sexual orientation is
rather more strongly heritable than female.

4.The shared family environment
has no effect on male sexual orientation but may have a small effect on female
sexual orientation.

5.There must also be non-genetic
factors influencing this trait, as monozygotic twins are still often discordant
(more often than concordant, in fact).

The fact that sexual orientation in males
and females is influenced by distinct sets of genetic variants is interesting
and leads to a fundamental insight: heterosexuality is not a single default
state. It emerges from distinct biological processes that actively match the
brain circuitry of (i) males or (ii) females to their chromosomal and gonadal sex so that most individuals who carry a Y chromosome are attracted to females
and most people who do not are attracted to males.

What is being regulated, biologically, is
not sexual orientation (whether you are attracted to people of the same or
opposite sex), but sexual preference (whether you are attracted to males or
females). Given how complex the processes of sexual differentiation of the brain are (involving the actions of many different genes), it is not surprising
that they can sometimes be impaired due to variation in those genes, leading to
a failure to match sexual preference to chromosomal sex. Indeed, we know of
many specific mutations that can lead to exactly such effects in other mammals
– it would be surprising if similar events did not occur in humans.

These studies are consistent with the idea
that sexual preference is a biological trait – an innate characteristic of an
individual, not strongly affected by experience or family upbringing. Not a
choice, in other words. We didn’t need genetics to tell us that – personal
experience does just fine for most people. But this kind of evidence becomes
important when some places in the world (like Uganda, recently) appeal to
science to claim (wrongly) that there is evidence that homosexuality is an
active choice and use that claim directly to justify criminalisation of
homosexual behaviour.

Importantly, the fact that sexual
orientation is only partly heritable
does not at all undermine the conclusion that it is a completely biological
trait. Just because monozygotic twins are not always concordant for sexual
orientation does not mean the trait is not completely innate. Typically,
geneticists use the term “non-shared environmental variance” to refer to
factors that influence a trait outside of shared genes or shared family
environment. The non-shared environment term encompasses those effects that
explain why monozygotic twins are actually less than identical for many traits
(reflecting additional factors that contribute to variance in the trait across
the population generally).

The terminology is rather unfortunate
because “environmental” does not have its normal colloquial meaning in this
context. It does not necessarily mean that some experience that an individual
has influences their phenotype. Firstly, it encompasses measurement error (just
the difficulty in accurately measuring the trait, which is particularly
important for behavioural traits). Secondly, it includes environmental effects
prior to birth (in utero), which may be especially important for brain
development. And finally, it also includes chance or noise – in this case,
intrinsic developmental variation that can have dramatic effects on the end-state
or outcome of brain development. This process is incredibly complex and noisy,
in engineering terms, and the outcome is, like baking a cake, never the same
twice. By the time they are born (when the buns come out of the oven), the
brains of monozygotic twins are already highly unique.

Genetic differences may thus change the probability of an outcome over many
instances, without determining the
specific outcome in any individual.

A useful analogy is to handedness.
Handedness is only moderately heritable but is effectively completely innate or
intrinsic to the individual. This is true even though the preference for using
one hand over the other emerges only over time. The harsh experiences of many
in the past who were forced (sometimes with deeply cruel and painful methods)
to write with their right hands because left-handedness was seen as aberrant –
even sinful – attest to the fact that the innate preference cannot readily be
overridden. All the evidence suggests this is also the case for sexual
preference.

What about concerns that these findings
could be used as justification for labelling homosexuality a disorder? These
are probably somewhat justified – no doubt some people will use it like that. And
that places a responsibility on geneticists to explain that just because
something is caused by genetic variants – i.e., mutations – does not mean it
necessarily should be considered a disorder. We don’t consider red hair a
disorder, or blue eyes, or pale skin, or – any longer – left-handedness. All of
those are caused by mutations.

The word mutation is rather loaded, but in
truth we are all mutants. Each of us carries hundreds of thousands of genetic
variants, and hundreds of those are rare, serious mutations that affect the
function of some protein. Many of those cause some kind of difference to our
phenotype (the outward expression of our genotype). But a difference is only
considered a disorder if it negatively impacts on someone’s life. And
homosexuality is only a disorder if society makes it one.

That figure is from reports of latest study (not yet published). See here for links to other large twin studies: http://www.wiringthebrain.com/2014/03/gay-genes-yeah-but-no-well-kind-of-but.html?showComment=1395734941794#c3768417674897587425 . The concordance rates and heritability estimates vary across a pretty wide range.

Does the Y chromosome really explain that much variance? I don't think that it is that simple. Consider, for example, people with androgen insensitivity syndrome: http://www.ncbi.nlm.nih.gov/books/NBK1429/

Kevin is correct. It is not juts the Y chromosome, but more specifically the SRY gene with the Testes Determining Factor (TDF). Androgen insensitivity among several other disorders are a failure of the mechanism for TDF to either properly function or act on its receptors. They are exceptions that prove the given function.

"Just because something reduces Darwinian fitness does not make it a disorder - those are based on completely different criteria. We do not diagnose or categorise people on evolutionary grounds."

Well, that's certainly an odd statement.

Would you say that a female who has polycystic ovaries or endo- metriosis resulting in blocked fallopian tubes doesn't suffer from any disorder? The conditions greatly reduce or prevent her ability to conceive.

Would you say a man with low sperm production or with impaired sperm motility, either making it unlikely he will be able to impregnate a mate, has a disorder?

You would answer "yes" to both the above scenarios, I am sure.

A man who has healthy sperm along with a functioning sperm delivery system yet who aims that sperm at an infertile target has a disorder no different from the polycystic woman or the healthy sperm-challenged male. The only difference is locale of the disorder. This time it's the brain.

Something is called a disorder, in clinical terms, if people suffer from it. Evolutionary fitness doesn't come into that definition. There are tons of traits that lower fitness that we don't consider disorders - like shyness, or recklessness, for example.

"Something is called a disorder, in clinical terms, if people suffer from it. "

Really? " Suffer from it" as in physically or emotionally or both?

Odd comment ...again, esp. from one trained as a scientist.

How about a person who is blind in one eye, like my aunt? She had some kind of an eye infection as a child and was lucky to retain vision in one eye. She learned to adjust to daily life with one good eye. However, a "condition" is responsible for blindness in one eye.

What of my father? High cholesterol and triglycerides? So far, no suffering at all. Nevertheless, modern medicine considers he has a condition that could kill him prematurely. It's a condition.

Myopia? I don't actually "suffer" from it aside from its being a pain to have to search for my glasses or bother to put in contact lenses, but were they lost to me, I'd not be safe nor would anyone else on the road. If I had to track and kill prey, my distance vision would severely hinder my success and I'd starve. It's a condition.

As for "shyness" or "recklessness" of the garden variety, are you sure these characteristics lower reproduction?

On the other hand, those on the extreme of the autism spectrum do indeed have some sort of condition preventing their socialization and thus their reproductive odds.

You're playing word games out of some sense of righteousness, I would imagine.

"A man who has healthy sperm along with a functioning sperm delivery system yet who aims that sperm at an infertile target has a disorder no different from the polycystic woman or the healthy sperm-challenged male. The only difference is locale of the disorder. This time it's the brain."

By your definition Ted, my husband has a brain disorder too. I'm infertile, so every time he aims his perfectly functioning junk my way it's destined for evolutionary failure. Also, so is every man who aims at post-menopausal women.

I doubt that homosexuality is innate (and I also doubt that handedness is). Babies are not born with sexual preference. It is more likely that homosexuality is developmental. Waddington's epigenetic landscape explains why it is so difficult to change a trait after it occurred. An example may be mental retardation in the deaf (that was considered innate in the past), it is prevented if communication (e.g. sign language) begins early, but if communication is delayed until after a critical period MR occur and is very difficult to reverse.

Thanks for your comment Guy. Actually, I agree - innate is not the best word, but it's hard to find a better one that captures the meaning. Clearly, sexual preference does not emerge until sexual interest emerges. And hand preference is also apparently fluid for a while before it becomes fixed - that does not mean it can be changed by intervening at an early stage, however. We may be witnessing a trajectory that is fairly fixed and already intrinsic to the individual, even though they have not yet reached the endpoint. Alternatively, it may be more fluid but based on internal processes, which are not sensitive to outside forces. Or, for some traits, experience may really be crucial during some critical period - I don't think there's any evidence that that is the case for either sexual preference or handedness.

Hmm.....can't really say much about sexuality, but handedness? Well according to my family, I naturally tended left until I broke my arm as a toddler. I was then taught to be right handed. I honestly don't feel like I've ever been any other way but right handed. If what I'm told is true, it does seem to suggest something about experiential tweaking of a trait. Just a thought

Why Bisexuality is ignored or is treated as a variant of homosexuality? essentialist researchers present as fact (as universal, ahistorical and acultural) a model of sexuality that is one among many possible models of sexuality, and that is particular to contemporary western culture.

The only alternative to including bisexuals in the homosexual group is to abandon a dichotomous model of homosexuality and (possibly) the concept of ‘sexual orientation’, and to acknowledge that sexuality is more fluid and messy than the dichotomous model suggests.

Some men identify firmly as heterosexual but have regularsex with other men (e.g., men in prison or in the armed forces and other men who might be labelled ‘situational homosexuals’ or men who have sex with men (MSM)). Some people identify with a particular sexual identity because of political or ideological reasons (e.g., political lesbians). Some people identify as bisexual but are in a long-term monogamous relationship with someone of a different sex. Some people feel that their engagement in particular sexual communities or practices is a more important indicator of their sexuality than the sex/gender of the people they have sex with (e.g.,somepeople who engagein BDSM). These are just a few examples of the complexities in how people identify their sexuality and experience and express their sexual desires. If these people were invited to participate in a biological study, how would they be classified? Which aspect of sexuality – how we label and identify our sexuality (now or in the past), how we behave (now or in the past), what we desire (now or in the past) – counts as ‘the truth’ of our sexuality? Typically, essentialist researchers ignore the meanings people give to their sexualities and attempt to classify them in terms of the dichotomous heterosexual/homosexual model.

Just found this (it was probably you who posted on twitter). This is fairly well written. My biggest gripe is that siblings can share between 0-100% of their genetic makeup. Due to random chance, the average percentage likely hovers around 50%, but random chance can result in any two sibs sharing substantially more or less than 50%.

I would also suggest, in the future, when dealing with those who like to claim that being gay is evolutionarily detrimental, to point out species which are evolutionarily successful, even though not every member is a potential breeding member. Social creatures, like wolves, and eusocial insects, actually benefit from non-breeding members, who partake in caring for the young. Evolution judges success by species, not by individual, so suggesting that homosexuality fails Darwinian tests shows a lack of understanding of how evolution works. In fact, most people I encounter that try to make this argument don't believe the theory of evolution either. They are trying to disprove two realities at the same time.